We propose here the Molecular and Genomic Imaging Center (MGIC) in response to a biomedical-community-wide need for flexible, cost-effective, high-resolution technology to identify and characterize variation in biological systems at the level of genomes and transcriptomes. We plan to help meet this need by developing the polymerase colony, or polony, technology. Polonies represent a highly parallel method of nucleic acid analysis that is realistic, close-at-hand, modular, and versatile. The primary mission of the MGIC is to efficiently integrate a diverse set of contributions from technology developers into a robust platform that can be smoothly disseminated to a variety of users with specialized clinical and biological interests. These are the main aims: (1) Highly parallel fluorescent in situ sequencing. (2) Single molecule profiling of the transcriptome, in particular of neural differentiation and of mammalian alternative splicing. (3) Direct molecular haplotyping and long-range sequence connectivity. (4) Characterization of DNA &RNA from single cells, in particular characterizing asymmetric cell division in mammalian stem cells. (5) Computational algorithms and systems modeling addressing combinatorial and spatial patterns in nucleic acid analysis. (6) An ELSI component focuses on issues of translation of technology to clinical applications and challenges to the concepts of anonymity.